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Disease Associations Discovered with Four IgG Subclasses

By Labmedica International staff writers
Posted on 08 Nov 2017
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Image: Immunostaining for immunoglobulin G4 (IgG4) in IgG4-related inflammatory aortic aneurysm; abundant IgG4-positive plasma cell infiltration (Photo courtesy of Shiga University of Medical Science).
Image: Immunostaining for immunoglobulin G4 (IgG4) in IgG4-related inflammatory aortic aneurysm; abundant IgG4-positive plasma cell infiltration (Photo courtesy of Shiga University of Medical Science).
Immunoglobulin G4-related disease (IgG4-RD) is a relatively newly defined disease entity that refers to a group of immune-mediated disorders that have certain histopathologic, serologic, and clinical features in common.

IgG4-RD is often associated with elevated serum IgG4. The discovery of IgG4-RD highlights the scarcity of literature examining elevations in other IgG subclasses and their potential associations to disease. Immunoglobulin G4-related disease (IgG4-RD) can involve one or multiple organs. Clinicians should also be alert to the possibility that IgG4-RD can mimic autoimmune rheumatic diseases such as systemic lupus erythematosus, Sjögren's syndrome (SS), or granulomatosis with polyangiitis.

Scientists at the Harvard Medical School (Boston, MA, USA) identified 552 patients with an isolated elevation of one of the IgG subclasses, and performed a systematic chart review to identify the diagnoses of those patients. They examined the distribution of diagnoses, using the Fisher's exact test to determine if a diagnosis was significantly associated with an isolated elevation in one of the subclasses.

The investigators found that autoimmune pancreatitis, aspirin-exacerbated respiratory disease (AERD), nasal polyps, eosinophilia, and celiac disease were significantly associated with an isolated elevation in IgG4. Hepatitis C and monoclonal gammopathy were significantly associated with isolated elevations in IgG1. Rheumatoid arthritis (RA) was associated with both an isolated elevation in IgG1 and IgG3. Hypothyroidism and irritable bowel syndrome (IBS) were significantly associated with isolated elevations in IgG2.

The authors concluded that their study confirmed some established associations between autoimmune pancreatitis, AERD, nasal polyps, and eosinophilia and elevated serum IgG4, and between monoclonal gammopathy and hepatitis C with elevated serum IgG1. It uncovered novel associations between RA and elevated IgG1 and IgG3, hypothyroidism and IBS and elevated IgG2, and between celiac disease and elevated IgG4. The study was published in the October 2017 issue of the journal Seminars in Arthritis and Rheumatism.

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